Metabolic Syndrome, Inflammation, Heart Rate Variability, and Fitness in Obese African American Youth

Purpose. The purposes of this dissertation were to (1) explore the relationships among fitness, heart rate variability (HRV), inflammation and components of the Metabolic Syndrome in obese African American youth participating in a supervised weight management program, (2) examine the effect of change in severity of obesity on these variables, and (3) identify predictors of weight loss. Method. This study consisted of a post-hoc analysis of existing pre and post-intervention data obtained from 50 African-American youth (70% female, aged 7-18 years). Anthropometric assessment of height, weight, waist circumference, systolic blood pressure, body mass index, body mass index percentile ranges, and relative body mass index were conducted. Laboratory measures included high-density lipoprotein cholesterol, triglycerides, fibrinogen, and C-reactive protein levels, and fasting and 2-hr postprandial insulin and glucose levels obtained during a mixed meal tolerance test for determination of impaired glucose tolerance and insulin resistance. Aerobic fitness was assessed by cardiopulmonary maximal treadmill exercise using the Branching Protocol (VO2max). Heart rate variability was measured with a 24-hour Holter monitor and measures of circadian fluctuation (SDNN), parasympathetic function (HF), and sympathetic/ parasympathetic balance (LF/HF ratio) were calculated. Measures were repeated at 6 months. Data were analyzed using descriptive statistics, Pearson’s correlation coefficient, non-parametric t-tests and multiple linear regression. Metabolic Syndrome was defined based on World Health Organization definition with age, gender, and race-specific cut-points. Results. Baseline measures revealed the following means: age 12.9 ± 2.9, weight 92.2 kg ± 28.4, relative body mass index 195.5 ± 42.4, HF 5.9 [ln(ms2)] ± 0.9, SDNN 128.1(ms) ± 38.2, LF/HF ratio 1.1 ± 0.1, VO2max 18.8 ± 4.5 mg/kg/min, C-reactive protein 0.75 mg/L ± 1.34, fibrinogen 372.64 mg/dl ± 71.12. The prevalence of the Metabolic Syndrome was 46% based on 39 subjects with complete data sets. The presence of the individual Metabolic Syndrome components, for the entire sample, was as follows: systolic blood pressure 44%, high density lipoprotein 20%, triglycerides 40%, impaired glucose tolerance 18%, insulin resistance 82%, and waist circumference 73%. Inflammation was common (elevated C-reactive protein 45%, elevated fibrinogen 42%). VO2max was positively correlated with HF (r = 0.41, p = 0.004) and SDNN (r = 0.39, p = 0.007) and negatively with fibrinogen (r =-0.53, p = 0.0002) and relative body mass index (r = -0.47, p = 0.0007). Relative body mass index was positively associated with C-reactive protein (r = 0.38, p = 0.01) and fibrinogen (r = 0.51, p = 0.003). Those with impaired glucose tolerance did not differ in HRV measures, fitness, or inflammation. Insulin resistance was associated with HF (p = 0.004) and fibrinogen (p = 0.02). Waist circumference was associated with LF/HF ratio (p = 0.02). Lower high density lipoprotein was associated with higher fibrinogen (p = 0.05). There were no significant differences in HRV, VO2max, or inflammation in youth with or without Metabolic Syndrome. Change in relative body mass index was associated with improved SDNN (r = 0.36, p = 0.04) and there was a trend toward better VO2max (r = -0.30, p = 0.07) and HF (r = 0.33, p = 0.07). Male gender and higher baseline fitness accounted for 28% of the variance in RBMI change. Conclusions. Metabolic Syndrome is common in obese youth, even in younger children. Insulin resistance, even in the absence of the Metabolic Syndrome, negatively affects HRV. Mild weight loss is associated with improvements in SDNN, a risk factor for sudden death. Strategies to improve weight loss and fitness in severely obese African American youth are needed

Associations Between Heart Rate Variability and Metabolic Syndrome Risk Factors

Metabolic syndrome (MetS) is a clustering of risk factors for cardiovascular disease (CVD) and type 2 diabetes (T2D) – two major causes of morbidity and mortality worldwide. Heart rate variability (HRV) is a non-invasive measure of cardiac autonomic regulation that predicts mortality and morbidity. Additionally, HRV is reduced in CVD, T2D and MetS. As such, HRV has potential to be a novel cardiometabolic risk factor to be included in clinical risk assessment. Therefore, the purpose of this thesis was to examine the relationships between MetS and HRV. A systematic review of cross-sectional studies examining relationships between HRV and MetS was completed to consolidate existing evidence and to guide future studies. This was followed by a cross-sectional investigation of time and frequency domain and nonlinear HRV in a population with MetS risk factors to determine which MetS risk factors were associated with HRV parameters. A pilot study was then conducted to study the feasibility of conducting a mobile health (mHealth) and exercise intervention in a rural population, which was followed by a 24-week randomized clinical trial to examine the effects of the interactive mHealth exercise intervention compared to standard of care exercise in participants with MetS risk factors. Overall, HRV was reduced in women with MetS compared to those without, though there were no differences in men. Waist circumference and lipid profiles were most commonly related to HRV parameters when studied cross-sectionally. The changes in waist circumference and fasting plasma glucose were associated with the change in HRV parameters when studied longitudinally. Following the intervention period, waist circumference and blood pressure were improved with no other changes in MetS risk factors. HRV parameters indicative of vagal activity were reduced over the intervention period, but there were no changes in other HRV parameters. There were no differences in changes between the intervention and control groups. In conclusion, MetS and HRV are associated in women but not men. However, there were no clear associations between MetS and HRV to suggest that HRV would be a valuable clinical risk factor

A systematic review and meta-analysis of the effects of flavanol-containing tea, cocoa and apple products on body composition and blood lipids: exploring the factors responsible for variability in their efficacy

Several randomized controlled trials (RCTs) and meta-analyses support the benefits of flavanols on cardiometabolic health, but the factors affecting variability in the responses to these compounds have not been properly assessed. The objectives of this meta-analysis were to systematically collect the RCTs-based-evidence of the effects of flavanol-containing tea, cocoa and apple products on selected biomarkers of cardiometabolic risk and to explore the influence of various factors on the variability in the responses to the consumption of these products. A total of 120 RCTs were selected. Despite a high heterogeneity, the intake of the flavanol-containing products was associated using a random model with changes (reported as standardized difference in means (SDM)) in body mass index (−0.15, p < 0.001), waist circumference (−0.29, p < 0.001), total-cholesterol (−0.21, p < 0.001), LDL-cholesterol (−0.23, p < 0.001), and triacylglycerides (−0.11, p = 0.027), and with an increase of HDL-cholesterol (0.15, p = 0.005). Through subgroup analyses, we showed the influence of baseline-BMI, sex, source/form of administration, medication and country of investigation on some of the outcome measures and suggest that flavanols may be more effective in specific subgroups such as those with a BMI ≥ 25.0 kg/m2, non-medicated individuals or by specifically using tea products. This meta-analysis provides the first robust evidence of the effects induced by the consumption of flavanol-containing tea, cocoa and apple products on weight and lipid biomarkers and shows the influence of various factors that can affect their bioefficacy in humans. Of note, some of these effects are quantitatively comparable to those produced by drugs, life-style changes or other natural products. Further, RCTs in well-characterized populations are required to fully comprehend the factors affecting inter-individual responses to flavanol and thereby improve flavanols efficacy in the prevention of cardiometabolic disorders

Obesity of Mentally Retarded Individuals: Prevalence, Characteristics, and Intervention

Research on the prevalence, characteristics, and treatment of obesity of mentally retarded individuals within the context of research findings with the obese nonretarded population was selectively reviewed. According to the available literature, obesity is a prevalent problem in the retarded population, and there is a greater incidence among females than males. The literature also suggests that obese retarded subjects as a group can be distinguished from their nonobese peers by their physical condition, but not by their eating style or personality characteristics. Behavioral self-control strategies have been found to be effective in producing weight loss in obese retarded children and adults. Further research is needed to reduce the high interindividual variability observed in treatment outcome studies and to address problems of long-term maintenance of weight loss

The metabolic inter-relationships between changes in waist circumference, triglycerides, insulin sensitivity and small, dense low-density lipoprotein particles with acute weight loss in clinically obese children and adolescents.

OBJECTIVE: Small, dense low-density lipoprotein (LDL) particles are highly atherogenic and strongly associated with obesity-related dyslipidemia. The metabolic inter-relationships between weight loss induced changes in waist circumference, triglycerides, insulin sensitivity and small-dense LDL particles in clinically obese children and adolescents have not been studied. METHODS: Seventy-five clinically obese boys and girls (standardized body mass index 3.07 ± 0.59, aged 8-18 years) were recruited. Anthropometric, body composition and cardiometabolic risk factors were measured pre- and post-weight loss. RESULTS: There were highly significant reductions in anthropometric, body composition and cardiometabolic risk factors. Triglyceride change was positively correlated with LDL peak particle density and percentage LDL pattern B changes (relative abundance of small, dense LDL particles). Multiple regression analyses showed that changes in triglyceride concentration accounted for between 24 and 18% of the variance in LDL peak particle density and percentage LDL pattern B change, respectively. Changes in waist circumference and insulin sensitivity did not predict these changes in LDL characteristics. CONCLUSION: Acute and highly significant weight loss significantly decreased LDL peak particle density and percentage LDL pattern B. The change in triglycerides was a strong predictor of LDL peak particle density and percentage LDL pattern B change

Cardiovascular risk reduction in insulin resistant states

Introduction: Insulin resistance is the hall mark of a number of pathological conditions and is thought to play a major role in the cardiovascular risk associated with them. This thesis critically evaluates two insulin resistant conditions - polycystic ovary syndrome (PCOS) and type 2 diabetes (T2DM) - where there are many unresolved issues. During the course of these studies, the effect of weight loss and medications in modifying cardiovascular risk in these conditions was evaluated.Methods: The first studies focused on a randomised open labelled parallel study of metformin and rimonabant in obese patients with PCOS. Subsquently, an extension to this study was undertaken where patients who were on rimonabant were changed over to metformin, whereas those on metformin were continued on metformin for another 3 months. As part of this study the effect of rimonabant and metformin on incretin hormones in patients with PCOS was studied.The next studies focused on a randomised double blind placebo controlled study on the pleotrophic effect of atorvastatin in patients with PCOS. Subsequent metformin therapy after atorvastatin treatment was undertaken. This study led to the investigation of the effect of simvastatin and atorvastatin on biological variation of lipids in patients with T2DM that has got implications in treating to lipid targets. A corollary to this study was whether the biological variation of LDL calculated using Friedewald formula differed from that of direct LDL.Results: In the first series of studies, after 12 weeks of rimonabant there was a significant reduction in anthropometric and metabolic parameters as well as biochemical hyperandrogenemia in patients with PCOS. There was no change in any of these parameters in the metformin treated group. In three months extension arm to this study, metformin maintained the weight loss as well as enhanced the metabolic and biochemical parameters achieved by treatment with rimonabant, compared to 6 months of metformin treatment alone. There was a significant and reversible increase in glucose-dependent insulinotropic polypeptide (GIF) levels after 3 months of rimonabant treatment. There were no changes in GIF or glucagon-like peptide-1 (GLP-1) levels with metformin.In the second series of studies it has shown that atorvastatin was effective in reducing inflammation, biochemical hyperandrogenemia and metabolic parameters in patients with polycystic ovary syndrome after a 12 week period compared to placebo. The subsequent effect of three months metformin treatment was augmented by atorvastatin pre-treatment compared to placebo pre-treatment. In the subsequent study it was shown that the coefficient of variation (CV) of TC, LDL, HDL and TG on simvastatin was significant but comparable to atorvastatin in patients with T2DM. However, subsequent directly measured LDL cholesterol was shown to be an order of magnitude more stable when taking equivalent doses of atorvastatin rather than simvastatin.Conclusion: Both weight loss using rimonabant and atorvastatin were effective in reducing biochemical hyperandrogenemia and metabolic profile in patients with PCOS. The effect of rimonabant might be partly mediated through modulating GIF levels

The effect of 12 weeks regular physical activity and vitamin E in the treatment of non-alcoholic steatohepatitis: A pilot study

Background: Despite the prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH), there was no treatment has been proven to be effective in these common diseases. Although many studies have shown that lifestyle modifications such as increasing physical activities and exercise could be effective in the treatment of these common diseases, the optimal strategy was still not determined. According to the beneficial effects of antioxidant agents in the treatment of NASH, vitamin E has been used for this purpose by some clinicians. We designed this study for assessing beneficial effects of regular physical activity on the biochemical and imaging responses in patients with NASH and comparing this with vitamin E as an accepted treatment for NASH. Materials and Methods: This study was Randomized and single-blind clinical trials were carried out in Gonbad-e Kavus through which a total of 30 consecutive patients with the ultra sonographic diagnosis of non-alcoholic steatohepatitis (NASH)were enrolled and randomized to one of the three groups: Vitamin E 800 mg/day, regular physical activity, or both. Results: In all treatment groups improvement in liver transaminases level, serum lipids and ultrasonographic grading of fatty liver occurred after three months of treatment. When these decrement was compared between the treatment groups, there was no statistically significant difference in the value of improvement between the three groups (ANOVA: p>0.5). I.e. all three interventions improved the biochemical and ultrasonographic finding of fatty liver in the same way. Both groups with regular exercise had significant mean weight loss in comparison with the vitamin E group (a mean decrease of 3.0 kg in exercise group, 5.8 kg in subjects on regular exercise plus vitamin E and 0.2 kg in vitamin E group, ANOVA: p=0.04). Conclusion: There were no significant differences between exercise and vitamin E alone or in combination regarding the reduction in the level of liver enzymes and sonographic evidences of fatty liver although both resulted in significant improvements in biochemical endpoints. This implies that physical activity could be considered as effective as vitamin E in the improvement of biochemical and ultrasonographic presentations of NASH and the addition of Vitamin E does not offer any benefits. According to the findings of this pilot study a full-powered study with a control group should be designed. © 2015, Iranian Association of Gastroenterology and Hepatology. All rights reserved